Torque, a developer of T-cell cancer therapeutics produced through its Deep-Priming™ technology platform said today it has created a manufacturing process that will produce its T-cell cancer therapies and deliver them to patients much more quickly and inexpensively than current methods.

The company announced that its Slipstream™ process for making Deep-Primed T-Cells is in place at the GMP facility of University of California, Davis, which has collaborated with the company on the manufacturing platform through a partnership whose value has not been disclosed.

The UC Davis GMP facility will produce Torque’s lead candidate, Deep IL-15 Primed T Cells, when the company launches its first clinical trial later this year in both solid and hematologic tumors.

“This is an advance over the conventional cell therapy approaches, which are open, complex, and extremely labor intensive,” Torque CEO Bart Henderson, told GEN. “The goal is to shorten manufacturing time. And ultimately one of the options that we have down the road is to decentralize manufacturing and bring it close to bedside.”

Henderson said Slipstream is designed to deliver substantially greater efficiency over current cell therapy manufacturing through savings in cost, time, and labor that Torque declines to quantify.

“We’re aiming for vein-to-vein manufacturing completed in four weeks. That’s an important benchmark in the clinic to physicians, as their patients are progressing on their disease. That’s an important goal,” Henderson added.

Engineered to operate as modular compact factories, the Slipstream production platform is semi-automated and fully closed—features that are intended to eliminate contamination risk between transfers, and which can dramatically reduce staffing requirements and the factory footprint, according to Torque.

Based in Cambridge, MA, Torque emerged from stealth mode in November 2017 when it announced the launch of its tech platform, and its $25 million in Series A financing from Flagship Pioneering.

Designing for Commercial Scale

Fabio Fachin, Ph.D., vp of cell therapy engineering and manufacturing for Torque, said the company began developing Slipstream by opting to design for commercial-scale immediately, with the goal of bypassing challenges to cell therapy manufacturing in the transition from clinical trials to commercialization. Among those challenges is variability, both in how operators oversee manufacturing, and in the final product.

“When you look at the process that we have, it uses automation end to end. We focus on keeping the product closed at any step, so that contamination and any related issue is eliminated. And the final product qualities are really just set by the automation strategy,” Dr. Fachin said.

Before joining Torque, Dr. Fachin held positions at Novartis’ now-shuttered  Cell and Gene Therapies unit, where he led the development of the cell enrichment and manufacturing process for Kymriah™ (tisagenlecleucel), commercially launched last year as the first CAR-T immunotherapy product to win FDA approval; and at Massachusetts General Hospital MGH/Johnson & Johnson, where he led the engineering of point-of-care cancer diagnostic platforms in a collaboration with Johnson & Johnson.

Slipstream is designed to manufacture Torque’s Deep-Primed Immune Cell Therapies using cells collected from patients through apheresis. Both T cells and monocytes are isolated, followed by a three-step process:

  • Monocytes are matured into dendritic cells that are used to prime the T cells with multiple tumor-associated antigens. No genetic engineering is involved, and the maturing is designed to produce a blend of CD4 and CD8 cells.
  • The T cells are expanded to produce several billion tumor- targeting-primed, high-viability CD4+ and CD8+ T cells.
  • Using proprietary bioengineering, Deep IL-15 is tethered to the surface of the antigen-primed T cells. Those cells are transferred to vials and frozen, completing a manufacturing process that is closed from end to end, with no open transfers between steps.

Slipstream’s production line can be used in both large-scale and decentralized manufacturing settings, Torque says, with the potential to move cell manufacturing to point-of-care. Production capacity can be expanded by adding additional arrays in Lego-like fashion.

“You can incubate these products right next to each other in a larger incubator farm,” Gerhard Bauer, professor of hematology/oncology and director of the GMP laboratory at the UC Davis Institute for Regenerative Cures. “And after that incubation step, you take them out, you go to a small processing area again. You finish your processing, your vialing, and you freeze.”

Semi-Automated Process

“This is a very interesting approach as compared to having to do a process in individual rooms that are reserved for this particular product for the entire period of manufacturing, which is an enormous cost saving, and it’s a much better utilization of space and personnel,” Bauer said.

Slipstream is a semi-automated manufacturing process; machines perform the steps overseen by an operator. Slipstream could become completely automated at some point in the future, though for now, the presence of an operator will enhance quality control, Bauer said.

“The process can be likened to a process that you will see in a regular blood banking operation: You use your sterile welders, your sterile connecting device, your tubing sealers, and those centrifuges,” said Bauer. He previously developed the clinical-grade cell manufacturing and transduction procedures used in the development of Strimvelis™, which received European Commission approval in 2016 as the first autologous ex vivo gene therapy for children with adenosine deaminase severe combined immunodeficiency (ADA-SCID).

“A lot of people are familiar with this process already, so you can take people that know how to work this and immediately transition them into the manufacturing of a life-saving product,” Bauer added.

Torque’s Deep-Primed T cells target multiple tumor antigens, and pharmacologically activate an immune response with anchored cytokines. A focused set of immunomodulators is tethered to the surface of Deep-Primed T cells—initially interleukin 15 (IL-15) and interleukin 12 (IL-12) cytokines, and toll-like receptor (TLR) agonists—that activate and focus both innate and adaptive immunity. By loading precise doses of cytokines onto the surface of T cells, Deep Priming focuses the immune response to target the tumor, without systemic exposure.

For the clinical trial of Deep IL-15 Primed T Cells, Torque plans to prime the cells with five tumor-associated antigens via cassette.

“We can modulate that cassette as much as we want,” Dr. Fachin said. “Right now, the five is really a starting point. The idea is that we will actually be able to refine a signature eventually, based on what will be relevant. And we will be able to either increase that number or decrease it. The idea is that you essentially have no restriction in that regard.”

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